Study of nuclear factor-2 erythroid related factor-2 activator, berberine, in paclitaxel induced peripheral neuropathy pain model in rats

J Pharm Pharmacol. 2019 May;71(5):797-805. doi: 10.1111/jphp.13047. Epub 2018 Dec 10.

Abstract

Objectives: The role of nuclear factor-2 erythroid related factor-2 (Nrf2) activator, berberine (BBR), has been established in rat model of streptozotocin induced diabetic neuropathy. Around 30-40% of cancer patients, on paclitaxel (PTX) chemotherapy develop peripheral neuropathy. The present study was contemplated with the aim of establishing the neuropathy preventive role of BBR, in paclitaxel induced peripheral neuropathy model in rats.

Methods: A total of 30 Wistar rats were divided into five groups as follows: Group I: dimethyl sulfoxide; Group II: PTX+ 0.9% NaCl; Group III: Amitriptyline (ATL) + PTX; Group IV: BBR (10 mg/kg) + PTX and Group V: BBR (20 mg/kg) + PTX. Animals were assessed for tail flick latency, tail cold allodynia latency, histopathological scores, oxidative stress parameters, and mRNA expression of the Nrf2 gene in the sciatic nerve.

Key findings: Berberine significantly increased the tail flick and tail cold allodynia latencies and significantly decreased the histopathological score. BBR reduced oxidative stress by significantly decreasing the lipid peroxidation, increasing the superoxide dismutase and reduced glutathione levels in the sciatic nerve. BBR also increased the mRNA expression of Nrf2 gene in rat sciatic nerve.

Conclusions: All of these results showed the neuropathy preventing role of BBR in PTX induced neuropathy pain model in rats.

Keywords: Nrf2 expression; animal model; berberine; paclitaxel neuropathy.

MeSH terms

  • Animals
  • Berberine / pharmacology*
  • Glutathione / metabolism
  • Lipid Peroxidation / drug effects
  • Male
  • Malondialdehyde / metabolism
  • Models, Animal
  • NF-E2-Related Factor 2 / metabolism*
  • Neuralgia / chemically induced
  • Neuralgia / drug therapy*
  • Neuralgia / metabolism
  • Neuralgia / prevention & control
  • Oxidative Stress / drug effects
  • Paclitaxel
  • Peripheral Nervous System Diseases / chemically induced
  • Peripheral Nervous System Diseases / drug therapy*
  • Peripheral Nervous System Diseases / metabolism
  • Peripheral Nervous System Diseases / prevention & control
  • RNA, Messenger
  • Rats
  • Rats, Wistar
  • Sciatic Nerve / drug effects*
  • Superoxide Dismutase / metabolism

Substances

  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • RNA, Messenger
  • Berberine
  • Malondialdehyde
  • Superoxide Dismutase
  • Glutathione
  • Paclitaxel